Combined and targeted drugs delivery system for colorectal cancer treatment: Conatumumab decorated, reactive oxygen species sensitive irinotecan prodrug and quercetin co-loaded nanostructured lipid carriers

• Main Authors: Youqiang Liu (Author), Hongxin Zhang (Author), Haijing Cui (Author), Futong Zhang (Author), Liyan Zhao (Author), Yibing Liu (Author), Qingju Meng (Author)
• Format: Book
• Published: Taylor & Francis Group, 2022-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1071-7544; 1521-0464; 10.1080/10717544.2022.2027573
• Keywords: colorectal cancer; irinotecan prodrug; lipid nanoparticles; reactive oxygen species sensitive; Therapeutics. Pharmacology; RM1-950
• Source: Drug Delivery, Vol 29, Iss 1, Pp 342-350 (2022)

Purpose Colorectal cancer (CRC) is the third most frequently diagnosed cancer and this study aimed to develop a conatumumab decorated, irinotecan prodrug and quercetin co-loaded delivery system for combined and targeted colorectal cancer treatment. Methods A conatumumab (C) decorated, irinotecan prodrug (I-p) and quercetin (Q) co-encapsulated NLC (C I-p/Q NLC) was developed. In vitro and in vivo antitumor efficiency of NLC was evaluated on CRC cells and mice xenograft. Results The results showed that the HT-29 cells uptake of C I-p/Q NLC was over 70%. Reactive oxygen species (ROS) sensitive irinotecan prodrug formulation showed improved drug release ability in hypoxic conditions. C I-p/Q NLC showed significantly higher cytotoxicity than non-decorated NLC, single drug-loaded NLC and free drugs. In vivo studies in a CRC-bearing model corroborated the capability of nanoparticles for the inhibition of cancer, leading to a reduction of tumor growth without systemic toxicity. Conclusion The conatumumab decorated, ROS sensitive prodrug contained combination nano-system is a promising platform for CRC therapy.